We have re-examined the thermodynamic parameters we have obtained for sequence-nonspecific DNA association and sequence-specific DNA associations with Cro protein. The association of Cro protein with nonspecific DNA at 15 degrees C has a ratio of deltaSo/deltaGo close to the value of the temperature dependence of the dielectric constant of water which is as predicted by simple electrostatic theories of ion hydration (Born) and ion association (Bjerrum). Plots of deltaH vs. deltaCp and deltaSo vs. deltaCp for the twenty association reactions studied fall into two characteristic correlation groups. These results suggest that there are at least two distinct conformational subclasses in specific Cro-DNA complexes, which are stabilized by different combinations of enthalpic and entropic contributions. In the maturation of the capsid of bacteriophage T4, gp23, the protein primarily comprising the precursor shell, undergoes proteolysis to gp23 and the particles expand 15-20%. We have now investigated the intermediate states of capsid maturation; the cleaved/unexpanded state and the uncleaved/expanded state, by differential scanning calorimetry (DSC) and cryo-electron microscopy. Combining these and earlier results, we conclude that the expansion of the cleaved precursor is the major stabilization in T4 capsid maturation. We have completed a detailed thermodynamic analysis of ligand-induced multiphasic thermal protein denaturation. This treatment shows that the multiple peaks observed in DSC experiments, when ligand is in short supply, arises from the substantial increase in the free ligand concentration due to ligand released by unfolding protein. It is shown for the case of a protein having two ligand binding sites, that the observed bimodal DSC thermogram arises primarily form the contribution of partially liganded species rather than from ligand-free and fully saturated native species as is commonly believed.